Thalassemic hemoglobinopathies.

Abstract

Hemoglobinopathies are due to changes in the normal amino acid sequence of globin. Thalassemias result from imbalance in the normal coordinated synthesis of the globin subunits that make up the hemoglobin tetramer. It is now apparent that a single globin gene can have coding region mutations which simultaneously produce a structural defect (hemoglobinopathy) and a biosynthetic defect (thalassemia). It is likely that two distinct mutations within the same gene can occur and produce a hemoglobinopathy with features of thalassemia. In this review the authors discuss such disorders and include the Hb Lepore and Constant Spring variants, hyper-unstable globins, mutations which create alternative sites for mRNA splicing, and amino acid substitutions likely to be associated with an additional thalassemia lesion within the same gene.